Long term depletion of serotonin leads to selective changes in glutamate receptor subunits

The present study was carried out to clarify possible modulation mechanism of serotonin (5-HT) on glutamatergic neurotransmission in the rat cerebral colter. 5-HT was depleted by a 5-HT metabolite blocker (para-chlorophenylal anine; pCPA) for a week. Receptor binding experiments using (S)-[H-3]alpha -amino-3-hydroxy-5-methylisoxazol-4-propionic acid (AMPA) showed a consider able increase in B-max value of the membrane samples prepared from the cere bral cortex of rats compared with that of control animals received saline. In contrast, B-max value of the [H-3]MK-801 binding experiments for NMDA re ceptor was not changed by pCPA-treatment, Changes in the density of each AM PA receptor subtype were examined in the cerebral cortex by immunoblot anal yses using antibodies against AMPA receptor subunits. The density of immuno reactive bands with receptor subtype specific antibodies against GluR2/3 an d GluR2 receptors was increased, whereas that of GluR1 receptors was decrea sed. Considering GluR2, receptor subtype inhibits Ca2+ influx into neurons, the present study suggests that 5-HT appears to modulate synaptic plastici ty by regulating the density of each AMPA receptor subtype. (C) 2000 Publis hed by Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.